1. Field of the Invention
The present invention relates to a process for preparing 4-aminodiphenyl-amines intermediates.
2. Related Art
4-Aminodiphenylamines are widely used as intermediates in the manufacture of alkylated derivatives having utility as antiozonants and antioxidants, as stabilizers for monomers and polymers, and in various specialty applications. For example, reductive alkylation of 4-aminodiphenylamine (4-ADPA) with methylisobutyl ketone provides N-(1,3-dimethylbutyl)-Nxe2x80x2-phenyl-p-phenylene-diamine, which is a useful antiozonant for the protection of various rubber products.
4-Aminodiphenylamine derivatives can be prepared in various ways. An attractive synthesis is the reaction of an optionally substituted aniline with an optionally substituted nitrobenzene in the presence of a base, as disclosed, for example, in U.S. Pat. No. 5,608,111 (to Stern et al.) and U.S. Pat. No. 5,739,403 (to Reinartz et al.).
U.S. Pat. No. 5,608,111 describes a process for the preparation of an optionally substituted 4-ADPA wherein in a first step optionally substituted aniline and optionally substituted nitrobenzene are reacted (coupled) in the presence of a base. In working examples, aniline and nitrobenzene are reacted in the presence of tetramethylammonium hydroxide as the base, and water and aniline are azeotropically removed during the coupling reaction.
International publication WO 00/35853 discloses a method of preparation of intermediates of 4-aminodiphenylamine by the reaction of aniline with nitrobenzene in a liquid medium where the reaction system consists of a solution of salts of true zwitterions with hydroxides. A combination of potassium hydroxide and betaine hydrate is exemplified. The reaction may take place in the presence of free oxygen.
EP publication 566 783 describes a method of manufacture of 4-nitrodiphenylamine by the reaction of nitrobenzene with aniline in the medium of a polar aprotic solvent in a strongly alkaline reaction system. A phase transfer catalyst such as tetrabutylammonium hydrogen sulfate is employed. This reference requires that the reaction be carried out in an oxygen-free atmosphere in order to prevent undesirable side reactions caused by oxidation.
U.S. Pat. No. 5,117,063 and International publication WO 01/14312 disclose processes processes for preparing 4-nitrodiphenylamine and 4-nitrosodiphenhlamine, using an inorganic base with crown ether, a phase transfer catalyst.
The objective of the present invention is to provide a superior method for producing one or more 4-ADPA intermediates by reacting aniline and nitrobenzene in the presence of a strong base and a phase transfer catalyst.
In brief summary, the primary embodiment of the present invention is for a method of producing one or more 4-aminodiphenylamine intermediates comprising the steps of:
(a) bringing an aniline or aniline derivative and nitrobenzene into reactive contact; and
(b) reacting the aniline and nitrobenzene in a confined zone at a suitable time and temperature, in the presence of a mixture comprising a strong base, an oxidant and a phase transfer catalyst selected from the group of compounds defined by (b) reacting the aniline and nitrobenzene in a confined zone at a suitable time and temperature, in the presence of a mixture comprising a strong base, an oxidant, and a phase transfer catalyst selected from the group of compounds defined by: 
xe2x80x83where R1, R2, R3 are the same or different and selected from any straight chain or branched alkyl group containing from C1 to C20, (R4)e is hydrogen for e=0, R4 is R1R2R3N+ for e=1 or 2, Y is alkyl, aryl , alkyl aryl or benzyl and substituted derivatives thereof, Z is a substituent selected from the group consisting of hydroxyl, halo, and other hetero atoms, X is an anionic moiety of the form fluoride, chloride, hydroxide, sulfate, hydrogensulfate, acetate, formate, nitrate, phosphate, hydrogen phosphate, dihydrogenphosphate, oxalate, carbonate, borate, tartrate, citrate, malonate and mixtures of said compounds, where a=the valence of the anionic moiety (1, 2 or 3), b and c are whole number integers of value 1, 2 or 3 and d is a whole number integer of value 0 to 4.
Other embodiments of the present invention encompass details about reaction mixtures and ratios of ingredients, particular phase transfer catalysts and particular strong bases, all of which are hereinafter disclosed in the following discussion of each of the facets of the present invention.
The present invention is directed to a method, as described above, for making intermediates of 4-ADPA that has superior yield and selectivity for those intermediates. Such intermediates comprise 4-nitroso- and/or 4-nitrodiphenylamines (p-NDPA and 4-NDPA, respectively) and salts thereof. The intermediates may then be hydrogenated to produce 4-aminodiphenylamine.
An example of a substituted and multifunctional phase transfer catalyst that is consistent with the above formula I is (2S, 3S)-bis(trimethylammonio)-1,4-butanediol dichloride. Other effective phase transfer catalysts fitting formula 1, in addition to those shown in the following examples, can be derived from examples in the literature, such as C. M. Starks and C. Liotta, Phase Transfer Catalysis, Principles and Techniques, Academic Press, 1978 and W. E. Keller, Fluka-Compendium, Vol. 1,2,3, Georg Thieme Verlag, New York, 1986, 1987, 1992.
Phase transfer catalysts known or believed to be particularly effective in the method of the invention include tetramethylammonium chloride, tetramethylammonium fluoride, tetramethylammonium hydroxide, bis-tetramethylammonium carbonate, tetramethylammonium formate and tetramethylammonium acetate; tetrabutylammonium hydrogensulfate and tetrabutylammonium sulfate; methyltributylammonium chloride; and benzyltrimethylammonium hydroxide (Triton B), tricaprylylmethylammonium chloride (Aliquat 336), tetrabutylammonium chloride, tetramethylammonium nitrate, cetyltrimethylammonium chloride and choline hydroxide .
Phase transfer catalysts of the present invention have several advantages over crown ethers, such as 18-crown-6, which were described as effective with alkali metal hydroxides in references such as U.S. Pat. No. 5,117,063 and International publication WO 01/14312 discussed above. The most obvious disadvantages of crown ethers are very high initial cost and high toxicity. In addition, most crown ethers have poor solubility in water, so they cannot be recovered for recycle with an aqueous base stream. Furthermore, the boiling points of crown ethers are high enough that they cannot be recovered by distillation without an extra distillation step. Even for the class of crown ethers that have good solubility in water, solubility in organics is also good, so that there will be a high loss to the organic product stream. Finally, crown ethers are known chelating agents, so that there is a high probability of unacceptable loss of expensive hydrogenation catalyst metal, due to complexation with the crown ether.
In the method of the invention, the molar ratio of phase transfer catalyst to nitrobenzene reactant is preferably from about 0.05:1 to about 1.2:1.
While aniline most effectively couples with nitrobenzene, certain aniline derivatives comprising amides such as formanilide, phenylurea and carbanilide as well as the thiocarbanilide can be substituted to produce 4-ADPA intermediates.
Although the reactants of the method of the invention are referred to as xe2x80x9canilinexe2x80x9d and xe2x80x9cnitrobenzenexe2x80x9d, and when it is 4-ADPA that is being manufactured the reactants are in fact aniline and nitrobenzene, it is understood that the reactants may also comprise substituted aniline and substituted nitrobenzene. Typical examples of substituted anilines that may be used in accordance with the process of the present invention include but are not limited to 2-methoxyaniline, 4-methoxy-aniline, 4-chloroaniline, p-toluidine, 4-nitroaniline, 3-bromoaniline, 3-bromo-4-aminotoluene, p-aminobenzoic acid, 2,4-diaminotoluene, 2,5-dichloroaniline, 1,4-phenylene diamine, 4,4xe2x80x2-methylene dianiline, 1,3,5-triaminobenzene, and mixtures thereof. Typical examples of substituted nitrobenzenes that may be used in accordance with the process of the present invention include but are not limited to o- and m-methylnitrobenzene, o- and m-ethylnitrobenzene, o- and m-methoxynitrobenzene, and mixtures thereof.
The method of the invention will hereinafter be described with reference to the manufacture of 4-ADPA itself, starting from aniline and nitrobenzene.
The molar ratio of aniline to nitrobenzene in the process according to the present invention is not particularly important, the process will be effective with an excess of either.
Strong bases particularly effective in the process of the present invention include potassium hydroxide, sodium hydroxide, cesium hydroxide, rubidium hydroxide and potassium-t-butoxide. It is preferred that mole ratio of strong base to nitrobenzene is greater than about 1:1. A particularly preferred mole ratio of strong base to nitrobenzene is about 2:1 to about 6:1.
The reactive contact of the process of the invention is carried out in the presence of an oxidant. The oxidant may be free oxygen, or an oxidizing agent such as hydrogen peroxide. Nitrobenzene may also function as an oxidizing agent.
The reactive contact may be carried out at a temperature of from about 20xc2x0 C. to about 125xc2x0 C. Other conditions for the reactive contact include pressures in the range of from about 20 mbar to about atmospheric. Reaction time is typically less than about 3.5 hours. It is advantageous to agitate the reaction mixture during the entire reaction.
The reaction of step (b) of the present method may be carried out in the presence of not greater than about 10:1 moles water to moles nitrobenzene. The amount of water does not include the water that hydrates with the reactants and/or with compounds formed in the process. When the reaction mixture comprising a strong base and a phase transfer catalyst is in aqueous solution, the reaction may be carried out with a continuous distillation of aniline-water azeotrope.
The aqueous phase may be reused to form a new reaction mixture. Fresh base is added to replace base lost by decomposition, by-product formation and solubility in the separated organic phase. Excess Aniline recovered by distillation from the reaction product mixture may be combined with make-up fresh aniline for recycle to form a new reaction mixture. Recovery of excess nitrobenzene is preferably carried out prior to hydrogenation of the 4-ADPA intermediate by a separation step and the recovered nitrobenzene may be hydrogenated to aniline for use in the process.
The method of the present invention for the preparation of 4-aminodiphenylamines intermediates may be conducted as a batch process or may be performed continuously using means and equipment well known to the skilled person.
The reactive contact in step (a) of the method of the invention may occur in a suitable solvent system. A suitable solvent system comprises a polar aprotic solvent. The polar aprotic solvent may be selected form the group consisting of dimethyl sulfoxide, benzyl ether, 1-Methyl-2-pyrrolidinone and N, N-dimethylformamide.
The invention includes a method where the strong base also functions as a phase transfer catalyst and the reaction may be in the absence of an alkali metal hydroxide. In that case the phase transfer catalyst may be selected from the group of compounds defined by: 
where R1, R2, R3 are the same or different and selected from any straight chain or branched alkyl group containing from C1 to C20, (R4)|e is hydrogen for e=0, R4 is R1R2R3N+ for e=1 or 2, Y is alkyl, aryl , alkyl aryl or benzyl and substituted derivatives thereof, Z is a substituent selected from the group consisting of hydroxyl, halo, and other hetero atoms, b and c are whole number integers of value 1, 2 or 3 and d is a whole number integer of value 0 to 4.
The invention is illustrated by the following examples.
Experimental conditions are detailed within individual examples. In all examples the charging of reactors was performed in open air resulting in some free oxygen being present during the reactions, except for experiments, where indicated, run for comparative purposes. No attempt was made to remove water from the reaction mixtures.
Yields of individual components were determined by external standard HPLC. Approximately 0.6 grams of material to be analyzed is accurately weighed into a 50-mL volumetric flask and diluted with a buffer solution containing 39% v/v water, 36% v/v acetonitrile, 24% v/v methanol and 1% v/v pH 7 buffer. The solution is injected through a 10 xcexcL loop onto a reversed phase Zorbax ODS HPLC column (250xc3x974.6 mm) using a binary gradient pumping system and the following elution gradient at a constant flow rate of 1.5 mL/minute:
Eluent A is 75% v/v water, 15% v/v acetonitrile and 10% v/v methanol. Eluent B is 60% v/v acetonitrile and 40% v/v methanol. Detection is UV at 254 nm.
Nitrobenzene conversion is calculated by sum addition of known components plus any unknown peaks (assigned an arbitrary mole weight value of 216, aniline+nitrobenzene) as analyzed. In some instances, sum conversion is greater than 100% due to the formation of derivatives from aniline only.
Selectivity is defined by the formula: (p-NDPA Yield+4-NDPA Yield)/Conversion where 4-NDPA is 4-nitrodiphenylamine and p-NDPA is 4-nitrosodiphenylamine.
In the tables: xe2x80x9cAn Recrxe2x80x9d refers to compounds from which aniline may be easily recovered and is a sum total of trans-azobenzene and azoxybenzene; xe2x80x9cOthersxe2x80x9d are aniline and nitrobenzene coupling by-products e.g. phenazine, N-oxy-phenazine, 2-NDPA, 4-phenazo-diphenylamine and any unknowns.
Experimental conditions are detailed within individual examples.